Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes.

Pereira, H. Anne; Erdem, İlknur; Pohl, Jan; Spitznagel, John K.

doi:10.1073/pnas.90.10.4733

Cited by 88 publications

(102 citation statements)

References 10 publications

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“…33). Azurocidin is an inactive member of the neutrophil serine proteases, with strong chemotactic activity toward monocytes (34). A ranking was made of proteins based on the largest difference in signal intensities relative to the reference protein between PLS and control (Supplemental Table 1).…”

Section: Resultsmentioning

confidence: 99%

Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses

Sørensen¹,

Clemmensen²,

Dahl³

et al. 2014

J. Clin. Invest.

146

173

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Papillon-Lefèvre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18 into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.

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Section: Resultsmentioning

confidence: 99%

Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses

Sørensen¹,

Clemmensen²,

Dahl³

et al. 2014

J. Clin. Invest.

146

173

View full text Add to dashboard Cite

show abstract

“…Cathepsin G was selected since it is a human neutrophil granule-derived protein with similar molecular weight to CAP37 and almost 35% sequence homology to CAP37 (Pereira et al, 1990a). Since CAP37 is a known LPS binding protein (Pereira et al, 1993), we included additional controls in which polymyxin B (2 g/ml, Sigma) was added to test samples containing CAP37, LPS, and cathepsin G. This control was included to confirm that the functional properties attributed to CAP37 in our studies were not due to endotoxin contamination of the rCAP37 preparation.…”

Section: Morphologic Determination Of Microglial Activationmentioning

confidence: 99%

“…It is a key mediator of monocyte (Pereira, 1995) and endothelial cell functions (Pereira, 2001) and promotes monocyte chemotaxis (Pereira et al, 1990b), adhesion of monocytes to endothelial cells, and activates endothelial cell protein kinase C, a critical second messenger (Pereira et al, 1996a). CAP37 was originally isolated from the granules of human polymorphonuclear leukocytes (PMN) and was shown to have strong antimicrobial activity particularly for gram-negative bacteria (Shafer et al, 1984;Pereira et al, 1993). Therefore, it has been traditionally considered part of the oxygen-independent killing mechanism and innate defense system of the host.…”

Section: Introductionmentioning

confidence: 99%

Activation of microglia: A neuroinflammatory role for CAP37

Pereira

Ruan

Kumar³

2002

Glia

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Recent evidence suggests that inflammation and immune function in the central nervous system (CNS) may play a considerable role in the progression of many neurodegenerative diseases. It is known that microglia, the CNS equivalent of peripheral blood monocytes, may be instrumental in causing neurotoxicity. However, the mediator(s) that activates microglia to produce toxic substances that orchestrate cell death has yet to be elucidated. We have identified a novel inflammatory molecule, cationic antimicrobial protein of molecular weight 37 kDa (CAP37), to the brains of patients dying from Alzheimer's disease. CAP37 is known to be a potent activator and regulator of monocyte function in the systemic circulation. We hypothesize that CAP37, a mediator previously shown to recruit and activate monocytes in the systemic circulation, may also play a role in CNS inflammation by modulating microglial function. Here we demonstrate that CAP37 is a chemoattractant for microglia and that CAP37-treated microglia express class II major histocompatibility antigens and produce proinflammatory cytokines and chemokines. We conclude that CAP37 has the ability to activate microglial cells and suggest that it has the potential to serve as a neuroinflammatory molecule. GLIA 41:64 -72, 2003.

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“…E. coli ML-35 and 35p were described previously (15 (49), Pancreatic human (50,51), pig (52), guinea pig (53). Residues identical to mouse iPLA2 are indicated in bold letters.…”

Section: Antimicrobial Testingmentioning

confidence: 99%

Bactericidal properties of murine intestinal phospholipase A2.

Harwig¹,

Tan²,

Qu³

et al. 1995

J. Clin. Invest.

237

149

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We purified a molecule from the murine small intestine that killed both Escherichia coli and Listeria monocytogenes, and identified it as intestinal phospholipase A2 (iPLA2) by NH2-terminal sequencing and enzymatic measurements. The ability of iPLA2 to kill. L monocytogenes was greatly enhanced by 5 mM calcium, inhibited by EGTA and abolished after reduction and alkylation, suggesting that enzymatic activity was required for iPLA2-mediated bactericidal activity. A mouse-avirulent phoP mutant, S. typhimunium 7953S, was 3.5-fold more susceptible to iPLA2 than its isogenic virulent parent, S. typhimurium 14028S (estimated minimal bactericidal concentrations 12.7±0.5 jig/ml vs. 43.9±4.5 jig/ml,

show abstract

Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes.

Cited by 88 publications

References 10 publications

Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses

Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses

Activation of microglia: A neuroinflammatory role for CAP37

Bactericidal properties of murine intestinal phospholipase A2.

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